A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Agents that inhibit PROTEIN KINASES.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.
The rate dynamics in chemical or physical systems.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A mitosporic Ophiostomataceae fungal genus, whose species Sporothrix schenckii is a well-known animal pathogen. The conidia of this soil fungus may be inhaled causing a primary lung infection, or may infect independently via skin punctures.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.
Established cell cultures that have the potential to propagate indefinitely.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A species of ciliate protozoa. It is used in biomedical research.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A group of compounds that contain the structure SO2NH2.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.
Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
The body of a fungus which is made up of HYPHAE.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Phosphoproteins are proteins that have been post-translationally modified with the addition of a phosphate group, usually on serine, threonine or tyrosine residues, which can play a role in their regulation, function, interaction with other molecules, and localization within the cell.
Cyclic nucleotides are closed-chain molecules formed from nucleotides (ATP or GTP) through the action of enzymes called cyclases, functioning as second messengers in various cellular signaling pathways, with cAMP and cGMP being the most prominent members.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Proteins prepared by recombinant DNA technology.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
The sum of the weight of all the atoms in a molecule.
A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Elements of limited time intervals, contributing to particular results or situations.
Transport proteins that carry specific substances in the blood or across cell membranes.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.

Nitric oxide stimulates the stress-activated protein kinase p38 in rat renal mesangial cells. (1/6323)

Nitric oxide (NO) has gained increased attention as a diffusible universal messenger that plays a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Recently, we reported that exogenous NO is able to activate the stress-activated protein kinase (SAPK) cascade in mesangial cells. Here, we demonstrate that exposure of glomerular mesangial cells to compounds releasing NO, including spermine-NO and (Z)-1- (N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen)-1-ium-1,2-diolate (MAHMA-NO), results in an activation of the stress-activated p38-mitogen-activated protein kinase (p38-MAPK) cascade as measured by the phosphorylation of the activator of transcription factor-2 (ATF2) in an immunocomplex kinase assay. Activation of the p38-MAPK cascade by a short stimulation (10 min) with the NO donor MAHMA-NO causes a large increase in ATF2 phosphorylation that is several times greater than that observed after stimulation with interleukin-1beta, a well-known activator of the p38-MAPK pathway. Time course studies reveal that MAHMA-NO causes rapid and maximal activation of p38-MAPK after 10 min of stimulation and that activation declines to basal levels within 60 min. The longer-lived NO donor spermine-NO causes a comparable rapid activation of the p38-MAPK pathway; however, the increased activation state of p38-MAPK was maintained for several hours before control values were reattained after 24 h of stimulation. Furthermore, the NO donors also activated the classical extracellular signal-regulated kinase (ERK) p44-MAPK cascade as shown by phosphorylation of the specific substrate cytosolic phospholipase A2 in an immunocomplex kinase reaction. Both MAHMA-NO and spermine-NO cause a rapid activation of p44-MAPK after 10 min of stimulation. Interestingly, there is a second delayed peak of p44-MAPK activation after 4-24 h of stimulation with NO donors. These results suggest that there is a differential activation pattern for stress-activated and mitogen-activated protein kinases by NO and that the integration of these signals may lead to specific cell responses.  (+info)

A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. (2/6323)

Two families of protein kinases that are closely related to Ste20 in their kinase domain have been identified - the p21-activated protein kinase (Pak) and SPS1 families [1-3]. In contrast to Pak family members, SPS1 family members do not bind and are not activated by GTP-bound p21Rac and Cdc42. We recently placed a member of the SPS1 family, called Misshapen (Msn), genetically upstream of the c-Jun amino-terminal (JNK) mitogen-activated protein (MAP) kinase module in Drosophila [4]. The failure to activate JNK in Drosophila leads to embryonic lethality due to the failure of these embryos to stimulate dorsal closure [5-8]. Msn probably functions as a MAP kinase kinase kinase kinase in Drosophila, activating the JNK pathway via an, as yet, undefined MAP kinase kinase kinase. We have identified a Drosophila TNF-receptor-associated factor, DTRAF1, by screening for Msn-interacting proteins using the yeast two-hybrid system. In contrast to the mammalian TRAFs that have been shown to activate JNK, DTRAF1 lacks an amino-terminal 'Ring-finger' domain, and overexpression of a truncated DTRAF1, consisting of only its TRAF domain, activates JNK. We also identified another DTRAF, DTRAF2, that contains an amino-terminal Ring-finger domain. Msn specifically binds the TRAF domain of DTRAF1 but not that of DTRAF2. In Drosophila, DTRAF1 is thus a good candidate for an upstream molecule that regulates the JNK pathway by interacting with, and activating, Msn. Consistent with this idea, expression of a dominant-negative Msn mutant protein blocks the activation of JNK by DTRAF1. Furthermore, coexpression of Msn with DTRAF1 leads to the synergistic activation of JNK. We have extended some of these observations to the mammalian homolog of Msn, Nck-interacting kinase (NIK), suggesting that TRAFs also play a critical role in regulating Ste20 kinases in mammals.  (+info)

Alzheimer's disease: clues from flies and worms. (3/6323)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells. (4/6323)

Genotoxic stress triggers the activation of several sensor molecules, such as p53, JNK1/SAPK and c-Abl, and occasionally promotes the cells to apoptosis. We previously reported that JNK1/SAPK regulates genotoxic stress-induced apoptosis in p53-negative U937 cells by activating caspases. c-Abl is expected to act upstream of JNK1/SAPK activation upon treatment with genotoxic stressors, but its involvement in apoptosis development is still unclear. We herein investigated the kinase activities of c-Abl and JNK1/SAPK during apoptosis elicited by genotoxic anticancer drugs and tumor necrosis factor (TNF) in U937 cells and their apoptosis-resistant variant UK711 cells. We found that the activation of JNK1/SAPK and c-Abl correlated well with apoptosis development in these cell lines. Unexpectedly, however, the JNK1/SAPK activation preceded the c-Abl activation. Moreover, the caspase inhibitor Z-Asp suppressed c-Abl activation and the onset of apoptosis but not the JNK1/SAPK activation. Interestingly, c-Abl tyrosine kinase inhibition by CGP 57148 reduced apoptosis without interfering with JNK1/SAPK activation. These results indicate that c-Abl acts not upstream of JNK1/ SAPK but downstream of caspases during the development of p53-independent apoptosis and is possibly involved in accelerating execution of the cell death pathway.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (5/6323)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. (6/6323)

The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced ( approximately 75%) its activity. These effects could be reversed by the action of protein phosphatase PP1. The inhibitory state of PDE4D3, engendered by ERK2 phosphorylation, was mimicked by the Ser579-->Asp mutant form of PDE4D3. In COS1 cells transfected to express PDE4D3, challenge with epidermal growth factor (EGF) caused the phosphorylation and inhibition of PDE4D3. This effect was blocked by the MEK inhibitor PD98059 and was not apparent using the Ser579-->Ala mutant form of PDE4D3. Challenge of HEK293 and F442A cells with EGF led to the PD98059-ablatable inhibition of endogenous PDE4D3 and PDE4D5 activities. EGF challenge of COS1 cells transfected to express PDE4D3 increased cAMP levels through a process ablated by PD98059. The activity of the Ser579-->Asp mutant form of PDE4D3 was increased by PKA phosphorylation. The transient form of the EGF-induced inhibition of PDE4D3 is thus suggested to be due to feedback regulation by PKA causing the ablation of the ERK2-induced inhibition of PDE4D3. We identify a novel means of cross-talk between the cAMP and ERK signalling pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP signalling.  (+info)

p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function. (7/6323)

Genetic screens in Drosophila have identified p50(cdc37) to be an essential component of the sevenless receptor/mitogen-activated kinase protein (MAPK) signaling pathway, but neither the function nor the target of p50(cdc37) in this pathway has been defined. In this study, we examined the role of p50(cdc37) and its Hsp90 chaperone partner in Raf/Mek/MAPK signaling biochemically. We found that coexpression of wild-type p50(cdc37) with Raf-1 resulted in robust and dose-dependent activation of Raf-1 in Sf9 cells. In addition, p50(cdc37) greatly potentiated v-Src-mediated Raf-1 activation. Moreover, we found that p50(cdc37) is the primary determinant of Hsp90 recruitment to Raf-1. Overexpression of a p50(cdc37) mutant which is unable to recruit Hsp90 into the Raf-1 complex inhibited Raf-1 and MAPK activation by growth factors. Similarly, pretreatment with geldanamycin (GA), an Hsp90-specific inhibitor, prevented both the association of Raf-1 with the p50(cdc37)-Hsp90 heterodimer and Raf-1 kinase activation by serum. Activation of Raf-1 via baculovirus coexpression with oncogenic Src or Ras in Sf9 cells was also strongly inhibited by dominant negative p50(cdc37) or by GA. Thus, formation of a ternary Raf-1-p50(cdc37)-Hsp90 complex is crucial for Raf-1 activity and MAPK pathway signaling. These results provide the first biochemical evidence for the requirement of the p50(cdc37)-Hsp90 complex in protein kinase regulation and for Raf-1 function in particular.  (+info)

Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-iun expression. (8/6323)

Activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases is an early response of cells upon exposure to DNA-damaging agents. JNK-mediated phosphorylation of c-Jun is currently understood to stimulate the transactivating potency of AP-1 (e.g., c-Jun/c-Fos; c-Jun/ATF-2), thereby increasing the expression of AP-1 target genes. Here we show that stimulation of JNK1 activity is not a general early response of cells exposed to genotoxic agents. Treatment of NIH 3T3 cells with UV light (UV-C) as well as with methyl methanesulfonate (MMS) caused activation of JNK1 and an increase in c-Jun protein and AP-1 binding activity, whereas antineoplastic drugs such as mafosfamide, mitomycin C, N-hydroxyethyl-N-chloroethylnitrosourea, and treosulfan did not elicit this response. The phosphatidylinositol 3-kinase inhibitor wortmannin specifically blocked the UV-stimulated activation of JNK1 but did not affect UV-driven activation of extracellular regulated kinase 2 (ERK2). To investigate the significance of JNK1 for transactivation of c-jun, we analyzed the effect of UV irradiation on c-jun expression under conditions of wortmannin-mediated inhibition of UV-induced stimulation of JNK1. Neither the UV-induced increase in c-jun mRNA, c-Jun protein, and AP-1 binding nor the activation of the collagenase and c-jun promoters was affected by wortmannin. In contrast, the mitogen-activated protein kinase/ERK kinase inhibitor PD98056, which blocked ERK2 but not JNK1 activation by UV irradiation, impaired UV-driven c-Jun protein induction and AP-1 binding. Based on the data, we suggest that JNK1 stimulation is not essential for transactivation of c-jun after UV exposure, whereas activation of ERK2 is required for UV-induced signaling leading to elevated c-jun expression.  (+info)

Calcium-calmodulin-dependent protein kinase type 2 (CAMK2) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways related to synaptic plasticity, learning, and memory. It is composed of four subunits, each with a catalytic domain and a regulatory domain that contains an autoinhibitory region and a calmodulin-binding site.

The activation of CAMK2 requires the binding of calcium ions (Ca^2+^) to calmodulin, which then binds to the regulatory domain of CAMK2, relieving the autoinhibition and allowing the kinase to phosphorylate its substrates. Once activated, CAMK2 can also undergo a process called autophosphorylation, which results in a persistent activation state that can last for hours or even days.

CAMK2 has many downstream targets, including ion channels, transcription factors, and other protein kinases. Dysregulation of CAMK2 signaling has been implicated in various neurological disorders, such as Alzheimer's disease, Parkinson's disease, and epilepsy.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

Calmodulin is a small, ubiquitous calcium-binding protein that plays a critical role in various intracellular signaling pathways. It functions as a calcium sensor, binding to and regulating the activity of numerous target proteins upon calcium ion (Ca^2+^) binding. Calmodulin is expressed in all eukaryotic cells and participates in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, metabolism, and cell cycle progression.

The protein contains four EF-hand motifs that can bind Ca^2+^ ions. Upon calcium binding, conformational changes occur in the calmodulin structure, exposing hydrophobic surfaces that facilitate its interaction with target proteins. Calmodulin's targets include enzymes (such as protein kinases and phosphatases), ion channels, transporters, and cytoskeletal components. By modulating the activity of these proteins, calmodulin helps regulate essential cellular functions in response to changes in intracellular Ca^2+^ concentrations.

Calmodulin's molecular weight is approximately 17 kDa, and it consists of a single polypeptide chain with 148-150 amino acid residues. The protein can be found in both the cytoplasm and the nucleus of cells. In addition to its role as a calcium sensor, calmodulin has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and cardiovascular disorders.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Cyclic AMP (cAMP)-dependent protein kinases, also known as protein kinase A (PKA), are a family of enzymes that play a crucial role in intracellular signaling pathways. These enzymes are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

PKA is composed of two regulatory subunits and two catalytic subunits. When cAMP binds to the regulatory subunits, it causes a conformational change that leads to the dissociation of the catalytic subunits. The freed catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity.

The cAMP-dependent protein kinases are activated in response to a variety of extracellular signals, such as hormones and neurotransmitters, that bind to G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). These signals lead to the activation of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The resulting increase in intracellular cAMP levels triggers the activation of PKA and the downstream phosphorylation of target proteins.

Overall, cAMP-dependent protein kinases are essential regulators of many fundamental cellular processes and play a critical role in maintaining normal physiology and homeostasis. Dysregulation of these enzymes has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Calcium-calmodulin-dependent protein kinase type 1 (CAMK1) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways involved in various cellular processes, including synaptic plasticity, learning, and memory. It is activated by the binding of calcium ions (Ca2+) and calmodulin, a ubiquitous calcium-binding protein, to its regulatory domain.

Once activated, CAMK1 phosphorylates various downstream target proteins, leading to changes in their activity or function. In the brain, CAMK1 is primarily expressed in neurons and has been implicated in the regulation of synaptic strength and transmission, as well as in the modulation of gene expression and cell survival. Dysregulation of CAMK1 has been associated with several neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) are a type of enzyme that add phosphate groups to other proteins, thereby modifying their function. These kinases are activated by cGMP, which is a second messenger molecule that helps transmit signals within cells. PKGs play important roles in various cellular processes, including smooth muscle relaxation, platelet aggregation, and cardiac contractility. They have been implicated in the regulation of a number of physiological functions, such as blood flow, inflammation, and learning and memory. There are two main isoforms of cGMP-dependent protein kinases, PKG I and PKG II, which differ in their tissue distribution, regulatory properties, and substrate specificity.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Benzylamines are a class of organic compounds that consist of a benzene ring attached to an amine group. The amine group (-NH2) can be primary, secondary, or tertiary, depending on the number of hydrogen atoms bonded to the nitrogen atom. Benzylamines are used in the synthesis of various pharmaceuticals, agrochemicals, and other organic compounds. They have a variety of biological activities and can act as central nervous system depressants, local anesthetics, and muscle relaxants. However, some benzylamines can also be toxic or carcinogenic, so they must be handled with care.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

"Sporothrix" is a genus of fungi that includes several species, the most well-known of which is "Sporothrix schenckii." This particular species is an environmental saprophyte, commonly found in soil, plant matter, and decaying organic material. It can cause a disease in humans and animals known as sporotrichosis, which is a subcutaneous infection that typically affects the skin and underlying tissue. The infection usually occurs after traumatic inoculation of the fungus through the skin, often from activities such as gardening or handling contaminated plant material.

The infection initially presents as a painless, nodular lesion at the site of inoculation, which can later ulcerate and spread to other parts of the body through lymphatic channels. Disseminated sporotrichosis is rare but can occur in immunocompromised individuals, affecting various organs such as the lungs, bones, and central nervous system.

Proper diagnosis of sporotrichosis involves direct examination and culture of clinical specimens, as well as serological tests and molecular techniques. Treatment typically includes oral antifungal medications such as itraconazole or posaconazole, although amphotericin B may be required in severe cases or in patients with compromised immune systems.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Calmodulin-binding proteins are a diverse group of proteins that have the ability to bind to calmodulin, a ubiquitous calcium-binding protein found in eukaryotic cells. Calmodulin plays a critical role in various cellular processes by regulating the activity of its target proteins in a calcium-dependent manner.

Calmodulin-binding proteins contain specific domains or motifs that enable them to interact with calmodulin. These domains can be classified into two main categories: IQ motifs and CaM motifs. The IQ motif is a short amino acid sequence that contains the consensus sequence IQXXXRGXXR, where X represents any amino acid. This motif binds to the C-lobe of calmodulin in a calcium-dependent manner. On the other hand, CaM motifs are longer sequences that can bind to both lobes of calmodulin with high affinity and in a calcium-dependent manner.

Calmodulin-binding proteins play crucial roles in various cellular functions, including signal transduction, gene regulation, cytoskeleton organization, and ion channel regulation. For example, calmodulin-binding proteins such as calcineurin and CaM kinases are involved in the regulation of immune responses, learning, and memory. Similarly, myosin regulatory light chains, which contain IQ motifs, play a critical role in muscle contraction by regulating the interaction between actin and myosin filaments.

In summary, calmodulin-binding proteins are a diverse group of proteins that interact with calmodulin to regulate various cellular processes. They contain specific domains or motifs that enable them to bind to calmodulin in a calcium-dependent manner, thereby modulating the activity of their target proteins.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Mitogen-Activated Protein Kinases (MAPKs) are a family of serine/threonine protein kinases that play crucial roles in various cellular processes, including proliferation, differentiation, transformation, and apoptosis, in response to diverse stimuli such as mitogens, growth factors, hormones, cytokines, and environmental stresses. They are highly conserved across eukaryotes and consist of a three-tiered kinase module composed of MAPK kinase kinases (MAP3Ks), MAPK kinases (MKKs or MAP2Ks), and MAPKs.

Activation of MAPKs occurs through a sequential phosphorylation and activation cascade, where MAP3Ks phosphorylate and activate MKKs, which in turn phosphorylate and activate MAPKs at specific residues (Thr-X-Tyr or Ser-Pro motifs). Once activated, MAPKs can further phosphorylate and regulate various downstream targets, including transcription factors and other protein kinases.

There are four major groups of MAPKs in mammals: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5/BMK1. Each group of MAPKs has distinct upstream activators, downstream targets, and cellular functions, allowing for a high degree of specificity in signal transduction and cellular responses. Dysregulation of MAPK signaling pathways has been implicated in various human diseases, including cancer, diabetes, neurodegenerative disorders, and inflammatory diseases.

I apologize for any confusion, but "Paramecium tetraurelia" is not a medical term. It is the scientific name of a species of ciliate protists, which are single-celled organisms commonly found in freshwater environments. These organisms are often studied in biology and microbiology as models for cellular and molecular processes. If you have any questions related to medical terminology or definitions, I would be happy to help with those instead.

Calcium-calmodulin-dependent protein kinase type 4 (CAMK4) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways related to synaptic plasticity, learning, and memory. It is activated by the binding of calcium ions and calmodulin, a regulatory protein that binds calcium ions, to its calcium-calmodulin binding domain.

Once activated, CAMK4 phosphorylates various downstream target proteins, including transcription factors, ion channels, and other kinases, thereby modulating their activities. This enzyme is widely expressed in various tissues, but it is particularly abundant in the brain, where it has been implicated in long-term potentiation (LTP), a form of synaptic plasticity that underlies learning and memory.

Mutations or dysregulation of CAMK4 have been associated with several neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Therefore, understanding the molecular mechanisms underlying CAMK4 activation and regulation is an important area of research in neuroscience and pharmacology.

Sulfonamides are a group of synthetic antibacterial drugs that contain the sulfonamide group (SO2NH2) in their chemical structure. They are bacteriostatic agents, meaning they inhibit bacterial growth rather than killing them outright. Sulfonamides work by preventing the bacteria from synthesizing folic acid, which is essential for their survival.

The first sulfonamide drug was introduced in the 1930s and since then, many different sulfonamides have been developed with varying chemical structures and pharmacological properties. They are used to treat a wide range of bacterial infections, including urinary tract infections, respiratory tract infections, skin and soft tissue infections, and ear infections.

Some common sulfonamide drugs include sulfisoxazole, sulfamethoxazole, and trimethoprim-sulfamethoxazole (a combination of a sulfonamide and another antibiotic called trimethoprim). While sulfonamides are generally safe and effective when used as directed, they can cause side effects such as rash, nausea, and allergic reactions. It is important to follow the prescribing physician's instructions carefully and to report any unusual symptoms or side effects promptly.

Calcium-binding proteins (CaBPs) are a diverse group of proteins that have the ability to bind calcium ions (Ca^2+^) with high affinity and specificity. They play crucial roles in various cellular processes, including signal transduction, muscle contraction, neurotransmitter release, and protection against oxidative stress.

The binding of calcium ions to these proteins induces conformational changes that can either activate or inhibit their functions. Some well-known CaBPs include calmodulin, troponin C, S100 proteins, and parvalbumins. These proteins are essential for maintaining calcium homeostasis within cells and for mediating the effects of calcium as a second messenger in various cellular signaling pathways.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Trifluoperazine is an antipsychotic medication that belongs to the class of drugs called phenothiazines. It works by blocking the action of dopamine, a neurotransmitter in the brain, and helps to reduce symptoms of schizophrenia such as hallucinations, delusions, paranoia, and disordered thought. Trifluoperazine may also be used to manage anxiety or agitation in certain medical conditions. It is available in the form of tablets for oral administration. As with any medication, trifluoperazine should be taken under the supervision of a healthcare provider due to potential side effects and risks associated with its use.

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

Myosin-Light-Chain Kinase (MLCK) is an enzyme that plays a crucial role in muscle contraction. It phosphorylates the regulatory light chains of myosin, a protein involved in muscle contraction, leading to the activation of myosin and the initiation of the contractile process. MLCK is activated by calcium ions and calmodulin, and its activity is essential for various cellular processes, including cytokinesis, cell motility, and maintenance of cell shape. In addition to its role in muscle contraction, MLCK has been implicated in several pathological conditions, such as hypertension, atherosclerosis, and cancer.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

p38 Mitogen-Activated Protein Kinases (p38 MAPKs) are a family of conserved serine-threonine protein kinases that play crucial roles in various cellular processes, including inflammation, immune response, differentiation, apoptosis, and stress responses. They are activated by diverse stimuli such as cytokines, ultraviolet radiation, heat shock, osmotic stress, and lipopolysaccharides (LPS).

Once activated, p38 MAPKs phosphorylate and regulate several downstream targets, including transcription factors and other protein kinases. This regulation leads to the expression of genes involved in inflammation, cell cycle arrest, and apoptosis. Dysregulation of p38 MAPK signaling has been implicated in various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, p38 MAPKs are considered promising targets for developing new therapeutic strategies to treat these conditions.

eIF-2 kinase is a type of protein kinase that phosphorylates the alpha subunit of eukaryotic initiation factor-2 (eIF-2) at serine 51. This phosphorylation event inhibits the guanine nucleotide exchange factor eIF-2B, thereby preventing the recycling of eIF-2 and reducing global protein synthesis.

There are four main subtypes of eIF-2 kinases:

1. HRI (heme-regulated inhibitor) - responds to heme deficiency and oxidative stress
2. PERK (PKR-like endoplasmic reticulum kinase) - activated by ER stress and misfolded proteins in the ER
3. GCN2 (general control non-derepressible 2) - responds to amino acid starvation
4. PKR (double-stranded RNA-activated protein kinase) - activated by double-stranded RNA during viral infections

These eIF-2 kinases play crucial roles in regulating cellular responses to various stress conditions, such as the integrated stress response (ISR), which helps maintain cellular homeostasis and promote survival under adverse conditions.

Tetradecanoylphorbol acetate (TPA) is defined as a pharmacological agent that is a derivative of the phorbol ester family. It is a potent tumor promoter and activator of protein kinase C (PKC), a group of enzymes that play a role in various cellular processes such as signal transduction, proliferation, and differentiation. TPA has been widely used in research to study PKC-mediated signaling pathways and its role in cancer development and progression. It is also used in topical treatments for skin conditions such as psoriasis.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Protein Kinase C-alpha (PKC-α) is a specific isoform of the Protein Kinase C (PKC) family, which are serine/threonine protein kinases that play crucial roles in various cellular processes such as proliferation, differentiation, and apoptosis. PKC-α is activated by diacylglycerol (DAG) and calcium ions (Ca2+). It is involved in signal transduction pathways related to cell growth, differentiation, and oncogenic transformation. Mutations or dysregulation of PKC-alpha have been implicated in several diseases including cancer, diabetes, and neurological disorders.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

Mitogen-Activated Protein Kinase 1 (MAPK1), also known as Extracellular Signal-Regulated Kinase 2 (ERK2), is a protein kinase that plays a crucial role in intracellular signal transduction pathways. It is a member of the MAPK family, which regulates various cellular processes such as proliferation, differentiation, apoptosis, and stress response.

MAPK1 is activated by a cascade of phosphorylation events initiated by upstream activators like MAPKK (Mitogen-Activated Protein Kinase Kinase) in response to various extracellular signals such as growth factors, hormones, and mitogens. Once activated, MAPK1 phosphorylates downstream targets, including transcription factors and other protein kinases, thereby modulating their activities and ultimately influencing gene expression and cellular responses.

MAPK1 is widely expressed in various tissues and cells, and its dysregulation has been implicated in several pathological conditions, including cancer, inflammation, and neurodegenerative diseases. Therefore, understanding the regulation and function of MAPK1 signaling pathways has important implications for developing therapeutic strategies to treat these disorders.

Calcium channels are specialized proteins that span the membrane of cells and allow calcium ions (Ca²+) to flow in and out of the cell. They are crucial for many physiological processes, including muscle contraction, neurotransmitter release, hormone secretion, and gene expression.

There are several types of calcium channels, classified based on their biophysical and pharmacological properties. The most well-known are:

1. Voltage-gated calcium channels (VGCCs): These channels are activated by changes in the membrane potential. They are further divided into several subtypes, including L-type, P/Q-type, N-type, R-type, and T-type. VGCCs play a critical role in excitation-contraction coupling in muscle cells and neurotransmitter release in neurons.
2. Receptor-operated calcium channels (ROCCs): These channels are activated by the binding of an extracellular ligand, such as a hormone or neurotransmitter, to a specific receptor on the cell surface. ROCCs are involved in various physiological processes, including smooth muscle contraction and platelet activation.
3. Store-operated calcium channels (SOCCs): These channels are activated by the depletion of intracellular calcium stores, such as those found in the endoplasmic reticulum. SOCCs play a critical role in maintaining calcium homeostasis and signaling within cells.

Dysregulation of calcium channel function has been implicated in various diseases, including hypertension, arrhythmias, migraine, epilepsy, and neurodegenerative disorders. Therefore, calcium channels are an important target for drug development and therapy.

Death-associated protein kinases (DAPKs) are a group of serine/threonine protein kinases that have been implicated in the regulation of programmed cell death, also known as apoptosis. There are several isoforms of DAPKs, including DAPK1, DAPK2, and DAPK3, each with distinct functions and regulatory mechanisms.

DAPK1 was the first to be identified and is perhaps the best studied. It plays a critical role in various forms of programmed cell death, including apoptosis, autophagy, and necroptosis. DAPK1 can be activated by various stimuli, such as calcium influx, oxidative stress, and DNA damage, and its activation leads to the phosphorylation of several downstream targets that contribute to the execution of cell death.

DAPK2 and DAPK3 have also been shown to regulate programmed cell death, although their functions are less well understood than those of DAPK1. DAPK2 has been implicated in the regulation of autophagy, while DAPK3 has been suggested to play a role in the regulation of both apoptosis and necroptosis.

Overall, DAPKs are important regulators of programmed cell death and have been implicated in various physiological and pathological processes, including development, neurodegeneration, ischemia-reperfusion injury, and cancer.

Cyclic AMP (cAMP)-dependent protein kinase catalytic subunits, also known as protein kinase A (PKA) catalytic subunits, are key enzymes that play a crucial role in intracellular signaling pathways. These subunits are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

The activation of cAMP-dependent protein kinase catalytic subunits occurs through a cascade of events that begins with the binding of extracellular signals to G protein-coupled receptors (GPCRs) on the cell surface. This binding event activates adenylyl cyclase, an enzyme that converts ATP to cAMP. The increased levels of cAMP then bind to and activate regulatory subunits of cAMP-dependent protein kinase, leading to the release and activation of the catalytic subunits.

Once activated, the cAMP-dependent protein kinase catalytic subunits phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity and function. This process is reversible, as phosphatases can dephosphorylate these residues and inactivate the target proteins.

There are four different isoforms of cAMP-dependent protein kinase catalytic subunits (PKA-Cα, PKA-Cβ, PKA-Cγ, and PKA-Cδ) that are encoded by separate genes but share a high degree of sequence homology. These isoforms can form homodimers or heterodimers with each other, and their expression patterns and subcellular localization can vary depending on the cell type and physiological context.

Overall, cAMP-dependent protein kinase catalytic subunits are essential regulators of many fundamental cellular processes, and their dysregulation has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Sequence homology, amino acid, refers to the similarity in the order of amino acids in a protein or a portion of a protein between two or more species. This similarity can be used to infer evolutionary relationships and functional similarities between proteins. The higher the degree of sequence homology, the more likely it is that the proteins are related and have similar functions. Sequence homology can be determined through various methods such as pairwise alignment or multiple sequence alignment, which compare the sequences and calculate a score based on the number and type of matching amino acids.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Cyclic guanosine monophosphate (cGMP) is a important second messenger molecule that plays a crucial role in various biological processes within the human body. It is synthesized from guanosine triphosphate (GTP) by the enzyme guanylyl cyclase.

Cyclic GMP is involved in regulating diverse physiological functions, such as smooth muscle relaxation, cardiovascular function, and neurotransmission. It also plays a role in modulating immune responses and cellular growth and differentiation.

In the medical field, changes in cGMP levels or dysregulation of cGMP-dependent pathways have been implicated in various disease states, including pulmonary hypertension, heart failure, erectile dysfunction, and glaucoma. Therefore, pharmacological agents that target cGMP signaling are being developed as potential therapeutic options for these conditions.

Mycelium is not a specifically medical term, but it is a biological term used in fungi and other organisms. Medically, it might be relevant in certain contexts such as discussing fungal infections. Here's the general definition:

Mycelium (my-SEE-lee-um) is the vegetative part of a fungus, consisting of a mass of branching, thread-like hyphae. It is the underground portion of the fungus that supports the growth of the organism and is often responsible for the decomposition of organic material. Mycelium can be found in various environments, including soil, water, and dead or living organisms.

Phosphoprotein phosphatases (PPPs) are a family of enzymes that play a crucial role in the regulation of various cellular processes by removing phosphate groups from serine, threonine, and tyrosine residues on proteins. Phosphorylation is a post-translational modification that regulates protein function, localization, and stability, and dephosphorylation by PPPs is essential for maintaining the balance of this regulation.

The PPP family includes several subfamilies, such as PP1, PP2A, PP2B (also known as calcineurin), PP4, PP5, and PP6. Each subfamily has distinct substrate specificities and regulatory mechanisms. For example, PP1 and PP2A are involved in the regulation of metabolism, signal transduction, and cell cycle progression, while PP2B is involved in immune response and calcium signaling.

Dysregulation of PPPs has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. Therefore, understanding the function and regulation of PPPs is important for developing therapeutic strategies to target these diseases.

Mitogen-Activated Protein Kinase Kinases (MAP2K or MEK) are a group of protein kinases that play a crucial role in intracellular signal transduction pathways. They are so named because they are activated by mitogens, which are substances that stimulate cell division, and other extracellular signals.

MAP2Ks are positioned upstream of the Mitogen-Activated Protein Kinases (MAPK) in a three-tiered kinase cascade. Once activated, MAP2Ks phosphorylate and activate MAPKs, which then go on to regulate various cellular processes such as proliferation, differentiation, survival, and apoptosis.

There are several subfamilies of MAP2Ks, including MEK1/2, MEK3/6 (also known as MKK3/6), MEK4/7 (also known as MKK4/7), and MEK5. Each MAP2K is specific to activating a particular MAPK, and they are activated by different MAP3Ks (MAP kinase kinase kinases) in response to various extracellular signals.

Dysregulation of the MAPK/MAP2K signaling pathways has been implicated in numerous diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, targeting these pathways with therapeutic agents has emerged as a promising strategy for treating various diseases.

Mitogen-Activated Protein Kinase 3 (MAPK3), also known as extracellular signal-regulated kinase 1 (ERK1), is a serine/threonine protein kinase that plays a crucial role in intracellular signal transduction pathways. It is involved in the regulation of various cellular processes, including proliferation, differentiation, and survival, in response to extracellular stimuli such as growth factors, hormones, and stress.

MAPK3 is activated through a phosphorylation cascade that involves the activation of upstream MAPK kinases (MKK or MEK). Once activated, MAPK3 can phosphorylate and activate various downstream targets, including transcription factors, to regulate gene expression. Dysregulation of MAPK3 signaling has been implicated in several diseases, including cancer and neurological disorders.

Cyclic AMP-dependent protein kinase type II (PKA II) is a subtype of cyclic AMP (cAMP)-dependent protein kinase, which is a crucial enzyme in many cellular processes. PKA II is composed of two regulatory subunits and two catalytic subunits. When cAMP levels are low, the regulatory subunits bind to and inhibit the catalytic subunits. However, when cAMP levels rise, cAMP molecules bind to the regulatory subunits, causing a conformational change that releases and activates the catalytic subunits.

The activated catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity, localization, or stability. PKA II is widely expressed in various tissues and plays a role in regulating diverse cellular functions such as metabolism, gene expression, cell growth, differentiation, and apoptosis.

PKA II is distinct from the other subtype of cAMP-dependent protein kinase, PKA I, in its regulatory subunit composition and tissue distribution. While both PKA I and PKA II contain identical catalytic subunits, they differ in their regulatory subunits: PKA I contains the RIα, RIβ, or RIIβ regulatory subunits, while PKA II contains the RIIα regulatory subunit. Additionally, PKA II is predominantly expressed in tissues such as the brain, heart, and skeletal muscle, whereas PKA I is more widely distributed throughout the body.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Protein Kinase C-delta (PKC-δ) is a specific isoform of the Protein Kinase C (PKC) family, which are serine/threonine protein kinases that play crucial roles in various cellular signaling pathways. PKC-δ is involved in several cellular processes such as proliferation, differentiation, apoptosis, and motility. It is activated by second messengers like diacylglycerol (DAG) and calcium ions (Ca2+), and its activation leads to the phosphorylation of specific target proteins, thereby modulating their functions. Aberrant regulation of PKC-δ has been implicated in various diseases, including cancer and neurodegenerative disorders.

Isoquinolines are not a medical term per se, but a chemical classification. They refer to a class of organic compounds that consist of a benzene ring fused to a piperidine ring. This structure is similar to that of quinoline, but with the nitrogen atom located at a different position in the ring.

Isoquinolines have various biological activities and can be found in some natural products, including certain alkaloids. Some isoquinoline derivatives have been developed as drugs for the treatment of various conditions, such as cardiovascular diseases, neurological disorders, and cancer. However, specific medical definitions related to isoquinolines typically refer to the use or effects of these specific drugs rather than the broader class of compounds.

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

JNK (c-Jun N-terminal kinase) Mitogen-Activated Protein Kinases are a subgroup of the Ser/Thr protein kinases that are activated by stress stimuli and play important roles in various cellular processes, including inflammation, apoptosis, and differentiation. They are involved in the regulation of gene expression through phosphorylation of transcription factors such as c-Jun. JNKs are activated by a variety of upstream kinases, including MAP2Ks (MKK4/SEK1 and MKK7), which are in turn activated by MAP3Ks (such as ASK1, MEKK1, MLKs, and TAK1). JNK signaling pathways have been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.

I'm sorry for any confusion, but "Peptide T" is not a widely recognized or established medical term. It appears that you might be referring to "T-20," which is also known as "Enfuvirtide." Enfuvirtide is a medication used in the treatment of HIV infection. It is a synthetic peptide that mimics a portion of the gp41 protein, which is a component of the viral envelope of HIV. By binding to this protein, enfuvirtide prevents the virus from infecting cells, providing an additional line of defense against the virus in combination therapy regimens.

If you meant something else by "Peptide T," please provide more context or clarify your question so I can give you a more accurate answer.

Serine is an amino acid, which is a building block of proteins. More specifically, it is a non-essential amino acid, meaning that the body can produce it from other compounds, and it does not need to be obtained through diet. Serine plays important roles in the body, such as contributing to the formation of the protective covering of nerve fibers (myelin sheath), helping to synthesize another amino acid called tryptophan, and taking part in the metabolism of fatty acids. It is also involved in the production of muscle tissues, the immune system, and the forming of cell structures. Serine can be found in various foods such as soy, eggs, cheese, meat, peanuts, lentils, and many others.

Phosphoproteins are proteins that have been post-translationally modified by the addition of a phosphate group (-PO3H2) onto specific amino acid residues, most commonly serine, threonine, or tyrosine. This process is known as phosphorylation and is mediated by enzymes called kinases. Phosphoproteins play crucial roles in various cellular processes such as signal transduction, cell cycle regulation, metabolism, and gene expression. The addition or removal of a phosphate group can activate or inhibit the function of a protein, thereby serving as a switch to control its activity. Phosphoproteins can be detected and quantified using techniques such as Western blotting, mass spectrometry, and immunofluorescence.

Cyclic nucleotides are formed by the intramolecular phosphoester bond between the phosphate group and the hydroxyl group at the 3'-carbon atom of the ribose sugar in a nucleotide. This creates a cyclic structure, specifically a cyclic phosphate. The most common cyclic nucleotides are cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These molecules function as second messengers in cells, playing crucial roles in various cellular signaling pathways related to metabolism, gene expression, and cell differentiation. The levels of cAMP and cGMP are tightly regulated by the activities of enzymes such as adenylate cyclase and guanylate cyclase for their synthesis, and phosphodiesterases for their degradation.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

I apologize, but I am not able to provide a medical definition for "Egtazic Acid" because it is not a term that is recognized in the field of medicine or pharmacology. It is possible that you may have meant "Egтарic Acid," which also does not have a specific medical meaning, or "Ethylene Glycol Tetraacetic Acid (EGTA)," which is a chemical compound used in research and medicine for its ability to bind calcium ions. If you have any other questions, I would be happy to try to help answer them.

AMP-activated protein kinases (AMPK) are a group of heterotrimeric enzymes that play a crucial role in cellular energy homeostasis. They are composed of a catalytic subunit (α) and two regulatory subunits (β and γ). AMPK is activated under conditions of low energy charge, such as ATP depletion, hypoxia, or exercise, through an increase in the AMP:ATP ratio.

Once activated, AMPK phosphorylates and regulates various downstream targets involved in metabolic pathways, including glycolysis, fatty acid oxidation, and protein synthesis. This results in the inhibition of energy-consuming processes and the promotion of energy-producing processes, ultimately helping to restore cellular energy balance.

AMPK has been implicated in a variety of physiological processes, including glucose and lipid metabolism, autophagy, mitochondrial biogenesis, and inflammation. Dysregulation of AMPK activity has been linked to several diseases, such as diabetes, obesity, cancer, and neurodegenerative disorders. Therefore, AMPK is an attractive target for therapeutic interventions in these conditions.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase type I (PKG I) is a major enzyme responsible for mediating the effects of cGMP, which is a second messenger molecule involved in various cellular signaling pathways. PKG I is a serine/threonine protein kinase that is activated by binding to cGMP.

PKG I exists in two isoforms, alpha and beta, which are encoded by separate genes but share a similar structure and function. The enzyme consists of a regulatory domain, which contains the cGMP-binding sites, and a catalytic domain, which carries out the phosphorylation of target proteins.

PKG I plays a critical role in regulating various physiological processes, including smooth muscle relaxation, cardiac contractility, platelet aggregation, and neuronal signaling. It does so by phosphorylating specific protein targets that control these processes, such as ion channels, enzymes, and cytoskeletal proteins.

Defects in PKG I function have been implicated in several human diseases, including pulmonary hypertension, heart failure, and erectile dysfunction. Therefore, PKG I is an important therapeutic target for the development of drugs to treat these conditions.

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

Cyclic AMP-dependent protein kinase RIα subunit, also known as PKA RIα or PRKAR1A, is a type of regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase (PKA) enzyme. PKA is a key enzyme in many cellular signaling pathways and is composed of two regulatory subunits and two catalytic subunits. The RIα subunit is one of the four different regulatory subunits (RIα, RIβ, RIIα, and RIIβ) that regulate PKA activity by binding to cAMP, which leads to the release and activation of the catalytic subunits.

The RIα subunit is encoded by the PRKAR1A gene and is primarily expressed in many tissues, including the brain, heart, and adrenal glands. Mutations in the PRKAR1A gene have been associated with several genetic disorders, such as Carney Complex, a rare autosomal dominant disorder characterized by multiple tumors and endocrine overactivity. The RIα subunit plays an essential role in regulating various cellular processes, including metabolism, differentiation, proliferation, and apoptosis.

I'm sorry for any confusion, but "Protamine Kinase" is not a widely recognized or established term in medical or biological sciences. Protamines are small, arginine-rich proteins found in the sperm cells of many organisms, and they play a crucial role in the packaging and protection of DNA during spermatogenesis.

Kinases, on the other hand, are enzymes that catalyze the transfer of phosphate groups from ATP to specific amino acids in proteins, thereby modulating their function, localization, or stability.

A search of scientific literature reveals only a few instances where "protamine kinase" is mentioned, usually in the context of potential regulatory mechanisms during sperm maturation or fertilization. However, there is no widely accepted or well-characterized enzyme known as "protamine kinase." Therefore, it would be challenging to provide a concise and accurate medical definition for this term.

Cytosol refers to the liquid portion of the cytoplasm found within a eukaryotic cell, excluding the organelles and structures suspended in it. It is the site of various metabolic activities and contains a variety of ions, small molecules, and enzymes. The cytosol is where many biochemical reactions take place, including glycolysis, protein synthesis, and the regulation of cellular pH. It is also where some organelles, such as ribosomes and vesicles, are located. In contrast to the cytosol, the term "cytoplasm" refers to the entire contents of a cell, including both the cytosol and the organelles suspended within it.

Recombinant fusion proteins are artificially created biomolecules that combine the functional domains or properties of two or more different proteins into a single protein entity. They are generated through recombinant DNA technology, where the genes encoding the desired protein domains are linked together and expressed as a single, chimeric gene in a host organism, such as bacteria, yeast, or mammalian cells.

The resulting fusion protein retains the functional properties of its individual constituent proteins, allowing for novel applications in research, diagnostics, and therapeutics. For instance, recombinant fusion proteins can be designed to enhance protein stability, solubility, or immunogenicity, making them valuable tools for studying protein-protein interactions, developing targeted therapies, or generating vaccines against infectious diseases or cancer.

Examples of recombinant fusion proteins include:

1. Etaglunatide (ABT-523): A soluble Fc fusion protein that combines the heavy chain fragment crystallizable region (Fc) of an immunoglobulin with the extracellular domain of the human interleukin-6 receptor (IL-6R). This fusion protein functions as a decoy receptor, neutralizing IL-6 and its downstream signaling pathways in rheumatoid arthritis.
2. Etanercept (Enbrel): A soluble TNF receptor p75 Fc fusion protein that binds to tumor necrosis factor-alpha (TNF-α) and inhibits its proinflammatory activity, making it a valuable therapeutic option for treating autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, and psoriasis.
3. Abatacept (Orencia): A fusion protein consisting of the extracellular domain of cytotoxic T-lymphocyte antigen 4 (CTLA-4) linked to the Fc region of an immunoglobulin, which downregulates T-cell activation and proliferation in autoimmune diseases like rheumatoid arthritis.
4. Belimumab (Benlysta): A monoclonal antibody that targets B-lymphocyte stimulator (BLyS) protein, preventing its interaction with the B-cell surface receptor and inhibiting B-cell activation in systemic lupus erythematosus (SLE).
5. Romiplostim (Nplate): A fusion protein consisting of a thrombopoietin receptor agonist peptide linked to an immunoglobulin Fc region, which stimulates platelet production in patients with chronic immune thrombocytopenia (ITP).
6. Darbepoetin alfa (Aranesp): A hyperglycosylated erythropoiesis-stimulating protein that functions as a longer-acting form of recombinant human erythropoietin, used to treat anemia in patients with chronic kidney disease or cancer.
7. Palivizumab (Synagis): A monoclonal antibody directed against the F protein of respiratory syncytial virus (RSV), which prevents RSV infection and is administered prophylactically to high-risk infants during the RSV season.
8. Ranibizumab (Lucentis): A recombinant humanized monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor A (VEGF-A), used in the treatment of age-related macular degeneration, diabetic retinopathy, and other ocular disorders.
9. Cetuximab (Erbitux): A chimeric monoclonal antibody that binds to epidermal growth factor receptor (EGFR), used in the treatment of colorectal cancer and head and neck squamous cell carcinoma.
10. Adalimumab (Humira): A fully humanized monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
11. Bevacizumab (Avastin): A recombinant humanized monoclonal antibody that binds to VEGF-A, used in the treatment of various cancers, including colorectal, lung, breast, and kidney cancer.
12. Trastuzumab (Herceptin): A humanized monoclonal antibody that targets HER2/neu receptor, used in the treatment of breast cancer.
13. Rituximab (Rituxan): A chimeric monoclonal antibody that binds to CD20 antigen on B cells, used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis.
14. Palivizumab (Synagis): A humanized monoclonal antibody that binds to the F protein of respiratory syncytial virus, used in the prevention of respiratory syncytial virus infection in high-risk infants.
15. Infliximab (Remicade): A chimeric monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.
16. Natalizumab (Tysabri): A humanized monoclonal antibody that binds to α4β1 integrin, used in the treatment of multiple sclerosis and Crohn's disease.
17. Adalimumab (Humira): A fully human monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.
18. Golimumab (Simponi): A fully human monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.
19. Certolizumab pegol (Cimzia): A PEGylated Fab' fragment of a humanized monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.
20. Ustekinumab (Stelara): A fully human monoclonal antibody that targets IL-12 and IL-23, used in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease.
21. Secukinumab (Cosentyx): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.
22. Ixekizumab (Taltz): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis and psoriatic arthritis.
23. Brodalumab (Siliq): A fully human monoclonal antibody that targets IL-17 receptor A, used in the treatment of psoriasis.
24. Sarilumab (Kevzara): A fully human monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis.
25. Tocilizumab (Actemra): A humanized monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell-induced cytokine release syndrome.
26. Siltuximab (Sylvant): A chimeric monoclonal antibody that targets IL-6, used in the treatment of multicentric Castleman disease.
27. Satralizumab (Enspryng): A humanized monoclonal antibody that targets IL-6 receptor alpha, used in the treatment of neuromyelitis optica spectrum disorder.
28. Sirukumab (Plivensia): A human monoclonal antibody that targets IL-6, used in the treatment

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Dietary calcium is a type of calcium that is obtained through food sources. Calcium is an essential mineral that is necessary for many bodily functions, including bone formation and maintenance, muscle contraction, nerve impulse transmission, and blood clotting.

The recommended daily intake of dietary calcium varies depending on age, sex, and other factors. For example, the recommended daily intake for adults aged 19-50 is 1000 mg, while women over 50 and men over 70 require 1200 mg per day.

Good dietary sources of calcium include dairy products such as milk, cheese, and yogurt; leafy green vegetables like broccoli and kale; fortified cereals and juices; and certain types of fish, such as salmon and sardines. It is important to note that some foods can inhibit the absorption of calcium, including oxalates found in spinach and rhubarb, and phytates found in whole grains and legumes.

If a person is unable to get enough calcium through their diet, they may need to take calcium supplements. However, it is important to talk to a healthcare provider before starting any new supplement regimen, as excessive intake of calcium can lead to negative health effects.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

The hippocampus is a complex, curved formation in the brain that resembles a seahorse (hence its name, from the Greek word "hippos" meaning horse and "kampos" meaning sea monster). It's part of the limbic system and plays crucial roles in the formation of memories, particularly long-term ones.

This region is involved in spatial navigation and cognitive maps, allowing us to recognize locations and remember how to get to them. Additionally, it's one of the first areas affected by Alzheimer's disease, which often results in memory loss as an early symptom.

Anatomically, it consists of two main parts: the Ammon's horn (or cornu ammonis) and the dentate gyrus. These structures are made up of distinct types of neurons that contribute to different aspects of learning and memory.

Protein Kinase C-epsilon (PKCε) is a serine-threonine protein kinase that belongs to the family of Protein Kinase C (PKC) enzymes. These enzymes play crucial roles in various cellular processes, including signal transduction, cell survival, differentiation, and apoptosis.

PKCε is specifically involved in regulating several signaling pathways related to inflammation, proliferation, and carcinogenesis. It can be activated by different stimuli such as diacylglycerol (DAG) and phorbol esters, which lead to its translocation from the cytosol to the plasma membrane, where it phosphorylates and modulates the activity of various target proteins.

Abnormal regulation or expression of PKCε has been implicated in several diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. Therefore, PKCε is considered a potential therapeutic target for these conditions, and inhibitors of this enzyme are being developed and tested in preclinical and clinical studies.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Protein Kinase C beta (PKCβ) is a serine-threonine protein kinase that belongs to the family of Protein Kinase C (PKC) enzymes. It plays a crucial role in various cellular processes, including signal transduction, cell survival, differentiation, and apoptosis. PKCβ is activated by diacylglycerol (DAG) and calcium ions (Ca2+), which results in its translocation from the cytosol to the plasma membrane, where it phosphorylates downstream target proteins.

There are two isoforms of PKCβ, PKCβI and PKCβII, which differ in their regulatory domains but have similar catalytic domains. PKCβ has been implicated in several diseases, including cancer, diabetes, and inflammatory disorders, making it a potential therapeutic target for drug development.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase type II (PKG II) is a subtype of cGMP-dependent protein kinases, which are enzymes that play a crucial role in the regulation of various cellular functions. PKG II is specifically expressed in certain tissues such as the smooth muscle and the brain.

The activation of PKG II occurs when cGMP binds to the regulatory subunit of the enzyme, leading to the release and activation of the catalytic subunit. Once activated, PKG II phosphorylates specific serine and threonine residues on target proteins, which in turn modulate their activity, localization, or stability.

PKG II has been implicated in several physiological processes, including smooth muscle relaxation, platelet aggregation, neuronal signaling, and cardiovascular function. Dysregulation of PKG II has been associated with various pathological conditions such as hypertension, pulmonary arterial hypertension, heart failure, and neurodegenerative disorders.

Biological models, also known as physiological models or organismal models, are simplified representations of biological systems, processes, or mechanisms that are used to understand and explain the underlying principles and relationships. These models can be theoretical (conceptual or mathematical) or physical (such as anatomical models, cell cultures, or animal models). They are widely used in biomedical research to study various phenomena, including disease pathophysiology, drug action, and therapeutic interventions.

Examples of biological models include:

1. Mathematical models: These use mathematical equations and formulas to describe complex biological systems or processes, such as population dynamics, metabolic pathways, or gene regulation networks. They can help predict the behavior of these systems under different conditions and test hypotheses about their underlying mechanisms.
2. Cell cultures: These are collections of cells grown in a controlled environment, typically in a laboratory dish or flask. They can be used to study cellular processes, such as signal transduction, gene expression, or metabolism, and to test the effects of drugs or other treatments on these processes.
3. Animal models: These are living organisms, usually vertebrates like mice, rats, or non-human primates, that are used to study various aspects of human biology and disease. They can provide valuable insights into the pathophysiology of diseases, the mechanisms of drug action, and the safety and efficacy of new therapies.
4. Anatomical models: These are physical representations of biological structures or systems, such as plastic models of organs or tissues, that can be used for educational purposes or to plan surgical procedures. They can also serve as a basis for developing more sophisticated models, such as computer simulations or 3D-printed replicas.

Overall, biological models play a crucial role in advancing our understanding of biology and medicine, helping to identify new targets for therapeutic intervention, develop novel drugs and treatments, and improve human health.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

The myocardium is the middle layer of the heart wall, composed of specialized cardiac muscle cells that are responsible for pumping blood throughout the body. It forms the thickest part of the heart wall and is divided into two sections: the left ventricle, which pumps oxygenated blood to the rest of the body, and the right ventricle, which pumps deoxygenated blood to the lungs.

The myocardium contains several types of cells, including cardiac muscle fibers, connective tissue, nerves, and blood vessels. The muscle fibers are arranged in a highly organized pattern that allows them to contract in a coordinated manner, generating the force necessary to pump blood through the heart and circulatory system.

Damage to the myocardium can occur due to various factors such as ischemia (reduced blood flow), infection, inflammation, or genetic disorders. This damage can lead to several cardiac conditions, including heart failure, arrhythmias, and cardiomyopathy.

Robinson A, Colbran R (2013). "Calcium/Calmodulin-Dependent Protein Kinases". In Lennarz W, Lane D (eds.). Encyclopedia of ... the calcium will bind to calmodulin. After the influx of calcium ions and the binding to calmodulin, pp60 SRC (a protein kinase ... Protein kinase C and ROC Kinase are involved in regulating Calcium ion intake; these Calcium ions, in turn stimulate a MYLK, ... a protein which depolymerizes actin stress fibers. Similar to ROCK, Protein Kinase C regulates MYLK via the CPI-17 protein, ...
This gene is also known by several other names: CMG 2 (CAMGUK protein 2), calcium/calmodulin-dependent serine protein kinase 3 ... "Entrez Gene: CASK Calcium/calmodulin-dependent serine protein kinase (MAGUK family)". Tarpey PS, Smith R, Pleasance E, Whibley ... Zhu ZQ, Wang D, Xiang D, Yuan YX, Wang Y (January 2014). "Calcium/calmodulin-dependent serine protein kinase is involved in ... July 2019). "Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of ...
Calcium/calmodulin dependent protein kinase IG is a protein that in humans is encoded by the CAMK1G gene. This gene encodes a ... "Entrez Gene: Calcium/calmodulin dependent protein kinase IG". Retrieved 2018-08-28. Takemoto-Kimura S, Terai H, Takamoto M, ... protein similar to calcium/calmodulin dependent protein kinase, however, its exact function is not known. [provided by RefSeq, ... a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK)". J. Biol. Chem. 278 (20): 18597-605. doi: ...
Calcium/calmodulin-dependent protein kinase ID is a protein in humans that is encoded by the CAMK1D gene on chromosome 10 ( ... "Entrez Gene: Calcium/calmodulin-dependent protein kinase ID". v t e (Articles with short description, Short description matches ... Human Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)) at the PDBe-KB. GRCh38: Ensembl release 89: ENSG00000183049 ... This gene encodes a member of the Ca2+/calmodulin-dependent protein kinase 1 subfamily of serine/threonine kinases. The encoded ...
... calcium/calmodulin-dependent protein kinase (CaM kinase) II delta". Hook SS, Means AR (2001). "Ca2+/CaM-dependent ... Calcium/calmodulin-dependent protein kinase type II delta chain is an enzyme that in humans is encoded by the CAMK2D gene. The ... product of this gene belongs to the serine/threonine protein kinase family and to the Ca2+/calmodulin-dependent protein kinase ... "Rad and Rad-related GTPases interact with calmodulin and calmodulin-dependent protein kinase II". J. Biol. Chem. 272 (18): ...
... is phosphorylated by the calcium-calmodulin-dependent protein kinase. MAPKAPK2 (mitogen-activated-protein kinase-activating ... that are phosphorylated by a variety of protein kinases. Ser40 is phosphorylated by the cAMP-dependent protein kinase. Ser19 ( ... "Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and ... Tyrosine hydroxylase is activated by phosphorylation dependent binding to 14-3-3 proteins. Since the 14-3-3 proteins also are ...
Activation of calcium/calmodulin-dependent protein kinase II in obesity mediates suppression of hepatic insulin signaling". ... and a calcium-induced apoptosis pathway, which involves an ER calcium-release channel IP3R, a calcium-sensitive protein kinase ... Tabas discovered a calcium-IP3R-CaMKII pathway plays a key role in glucagon-mediated excessive hepatic glucose production, ... One notable finding showed a critical link between the PERK / CHOP branch of the stress Unfolded protein response (UPR) ...
Picciotto, M. R.; Czernik, A. J.; Nairn, A. C. (15 December 1993). "Calcium/calmodulin-dependent protein kinase I. cDNA cloning ... "Calcium/calmodulin-dependent protein kinase I - cDNA cloning and identification of autophosphorylation site". J. Biol. Chem. ... work with Paul Greengard at Rockefeller University where she cloned the gene for calcium/calmodulin-dependent protein kinase 1 ...
This sudden increase in cytoplasmic calcium activates Ca2+/calmodulin-dependent protein kinase (CaMKII). Activated CaMKII ... January 2011). "Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling". EMBO Reports. 12 (1): 43 ... Ren J, Li Y, Kufe D (May 2002). "Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin ... June 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes to Cells. ...
"CAMK2A calcium/calmodulin dependent protein kinase II alpha [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. ... β CAMKIIδ CAMKIIγ CAMKIII CAMKIV CAMKV CaM kinase like vesicle associated SCAMK Ca2+/calmodulin-dependent protein kinase kinase ... CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. ... Hudmon A, Schulman H (2002-06-01). "Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and ...
CAMK2G and CAMK2D belong to the same calcium/calmodulin dependent protein kinase subfamily. These kinases play important roles ... Including the activation of ERK and other mitogen-activated protein kinases. eNOS or endothelial nitric oxide synthase ... Mifflin, L.; Ofengeim, D.; Yuan, J. (2020). "Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target". Nature ... MBP also disrupts the balanced expression of ERα and ERβ, leading to the dominant expression of the ERβ protein in cancer cells ...
Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (March 1997). "Molecular ... which contain residues that can be directly modified by a series of protein kinases and protein phosphatases, as well as ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ... A voltage-dependent flow of sodium (Na+), calcium (Ca2+), and potassium (K+) ions into and out of the cell is made possible by ...
"Calcium/calmodulin-dependent protein kinase II phosphorylation drives synapse-associated protein 97 into spines". The Journal ... is the influx of calcium through the NMDA receptors and the resultant activation of Ca2+/calmodulin-dependent protein kinase ( ... element-binding protein through a phosphatidylinositol 3-kinase-dependent stimulation of the mitogen-activated protein kinase ... "Long-term potentiation is associated with an increased activity of Ca2+/calmodulin-dependent protein kinase II". The Journal of ...
"Entrez Gene: CAMK2B calcium/calmodulin-dependent protein kinase (CaM kinase) II beta". Walikonis RS, Oguni A, Khorosheva EM, ... The enzyme belongs to the serine/threonine protein kinase family and to the Ca2+/calmodulin-dependent protein kinase subfamily ... Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene. ... Sequence analyses of human brain calcium/calmodulin-dependent protein kinase II". Mol. Biol. Rep. 28 (1): 35-41. doi:10.1023/A: ...
... downstream calcium effectors are the calcium-binding calmodulin protein and downstream calmodulin-dependent protein kinases I ... Calmodulin dependent kinase II was shown to be the protein responsible for converting the Ca2+ influx signal into inhibition of ... Li, Nan; Wang, Chunmei; Wu, Yanan; Liu, Xingguang; Cao, Xuetao (2009-01-30). "Ca2+/Calmodulin-dependent Protein Kinase II ... suggesting checkpoints require a calcium-dependent signaling mechanism Entry into S-phase is calcium dependent. Depleting ...
... resulting in a calcium influx into the SCN. Calcium induces the activity of Ca2+/calmodulin-dependent protein kinases, ... and Ca2+/calmodulin-dependent protein kinases on the Serine 133 residue. When activated, CREB protein recruits other ... This protein kinase translocates to the cell nucleus, where it activates a CREB protein. The activated CREB protein then binds ... Abnormalities of a protein that interacts with the KID domain of CREB, the CREB-binding protein, (CBP) is associated with ...
Like neuroligins, neurexins possess a PDZ-domain that associates with CASK (Calcium-calmodulin-dependent protein kinase). In ... Cadherins are calcium- dependent, homophilic cell adhesion molecules that form complexes with cytosolic partners known as ... This interaction, mediated by ephrin A3/EphA4 signaling, induces the recruitment and activation of cyclin-dependent kinase 5 ( ... Components of this complex bind to a number of different scaffolding proteins, phosphotases, kinases, and receptors. Classical ...
In an experiment using virus-induced gene silencing of two calcium-dependent protein kinases (CDPKs) in a wild tobacco ( ... are turned on by Ca2+ dependent protein kinases. In Arabidopsis, over expression of the IQD1 calmodulin-binding transcriptional ... This increase in cytosolic concentration activates target proteins such as Calmodulin and other binding proteins. Downstream ... When fatty acid amides are present in insect saliva, the mitogen-activated protein kinases (MAPKs) are activated. These genes ...
"Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human ... "Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human ... "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome ... KDR+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
1999). "Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through ... Membrane protein MLC1 is a protein that in humans is encoded by the MLC1 gene. MLC1 (also called WKL1) is the only human gene ... homology to other proteins suggests that it may be an integral membrane transport protein. Mutations in this gene have been ... The MLC1 protein contains six putative transmembrane domains (S1-S6) and a pore region (P) between S5 and S6. Furthermore, MLC1 ...
... for nuclear calcium oscillations and a nuclear localized complex comprising a calcium-and-calmodulin dependent protein kinase ... and calmodulin-dependent protein kinase CCaMK. Moreover, the role of CYCLOPS, initially annotated as a protein with unknown ... Deregulation of a Ca2+/calmodulin-dependent kinase leads to spontaneous nodule development. Nature Volume: 441 Issue: 7097 ... The Parniske lab discovered that CYCLOPS is an interactor and phosphorylation substrate of the calcium- ...
These include calcium-dependent calmodulin, CaMKII (calmodulin-dependent protein kinase II), PKC (Protein Kinase C), PKA ( ... Calcium influx into the cell through NMDA receptors binds to calmodulin and activates the Ca2+/calmodulin-dependent protein ... Protein Kinase A), Protein Phosphatase-1 (PP-1), and Fyn tyrosine kinase. Certain signallers, such as CaMKII, are upregulated ... The activation of the RhoA protein will activate ROCK, a RhoA kinase, which leads to the stimulation of LIM kinase, which in ...
Ca2+/calmodulin-dependent protein kinase II-protein phosphatase 1 switch facilitates specificity in postsynaptic calcium ... calmodulin-dependent protein kinase II (CaMKII), which leads to LTP. The difference in Ca2+ concentration required for a cell ... in the phosphorylation of isocitrate dehydrogenase and in the activation of the calmodulin-dependent protein kinase II (CAMKII ... called MAPK kinase, or MAPKK. Similarly, MAPKK is activated by MAPKK kinase, or MAPKKK. These kinases are sequentially ...
"Liprinalpha1 degradation by calcium/calmodulin-dependent protein kinase II regulates LAR receptor tyrosine phosphatase ... The protein encoded by this gene is a member of the LAR protein tyrosine phosphatase-interacting protein (liprin) family. ... Protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 1 has been shown to ... "Entrez Gene: PPFIA1 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 1 ...
Ca2+ quickly enters and binds to calmodulin. Calmodulin activates calcium/calmodulin-dependent protein kinase II (CaMKII), ... and calcium ions. Calcium ion entry into the presynaptic terminal causes the presynaptic release of glutamate, which diffuses ... This gives the NMDAR the property of being voltage-dependent, in that it requires strong postsynaptic depolarization to allow ...
... calmodulin-dependent protein kinase (CAMK) subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) ... calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase". J. Biol. Chem. 273 ... calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine ... calmodulin-dependent protein kinase kinase alpha by cAMP-dependent protein kinase: I. Biochemical analysis". J. Biochem. 130 (4 ...
Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase". J. Biol. Chem. 273 ... Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein ... Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly ...
Ng J, Rashid AJ, So CH, O'Dowd BF, George SR (January 2010). "Activation of calcium/calmodulin-dependent protein kinase IIalpha ... dual functional regulation by G protein-coupled receptor kinase 2". The Journal of Biological Chemistry. 285 (45): 35092-103. ... Hasbi A, Fan T, Alijaniaram M, Nguyen T, Perreault ML, O'Dowd BF, George SR (December 2009). "Calcium signaling cascade links ... In comparison, signalling of the homologous D5-D2 receptor heteromer involves the influx of extracellular calcium. The D1-D2 ...
This gene provides instructions for making calcium/calmodulin dependent serine protein kinase (CASK), a protein that is ... "Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by down ... a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with ... a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with ...
... calcium/calmodulin-dependent protein kinase kinase 2, beta". "CAMK1 - Calcium/calmodulin-dependent protein kinase type 1 ... calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine ... July 2005). "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase ... and to the Ca++/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent ( ...
2005). "Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B ... 2001). "Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)- ... portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. [number ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ...
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve ... in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. ... Calcium-Calmodulin Protein Kinase II; Calcium-Calmodulin-Dependent PK Type II; Calcium-Calmodulin-Dependent Protein Kinase Type ... Calcium-Calmodulin Dependent Protein Kinase II beta; Calcium-Calmodulin Dependent Protein Kinase II delta; Calcium-Calmodulin ...
Robinson A, Colbran R (2013). "Calcium/Calmodulin-Dependent Protein Kinases". In Lennarz W, Lane D (eds.). Encyclopedia of ... the calcium will bind to calmodulin. After the influx of calcium ions and the binding to calmodulin, pp60 SRC (a protein kinase ... Protein kinase C and ROC Kinase are involved in regulating Calcium ion intake; these Calcium ions, in turn stimulate a MYLK, ... a protein which depolymerizes actin stress fibers. Similar to ROCK, Protein Kinase C regulates MYLK via the CPI-17 protein, ...
Calcium/calmodulin dependent serine protein kinase (CASK). My 5-year-old daughter, Angelina, is living with CASK-gene related ...
Protein Serine-Threonine Kinases * Ribosomal Protein S6 Kinases * Calcium-Calmodulin-Dependent Protein Kinases ... and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), ... Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase Proc ... This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream ...
50: 1850-1855, 1996). In the present study, we examined the role of protein t … ... Calcium-Calmodulin-Dependent Protein Kinases * Mitogen-Activated Protein Kinases * Tetradecanoylphorbol Acetate * Bradykinin ... we examined the role of protein tyrosine phosphorylation and the mitogen-activated protein kinases, ERK1/2,in mediating BK- ... In contrast, protein kinase C inhibition or depletion had no effect on BK-induced c-fos mRNA, AP-1-DNA binding activity, or DNA ...
calcium/calmodulin-dependent protein kinase II gamma; N/A Antigen. Calcium/Calmodulin Dependent Protein Kinase II Gamma (CAMK2g ... Calcium/Calmodulin Dependent Protein Kinase II Gamma (CAMK2g) ; CAMK2g Applications. Immunohistochemistry (IHC), ELISA, EIA, ... This is an antibody designed to detect Calcium/Calmodulin Dependent Protein Kinase II Gamma (CAMK2g) ; CAMK2g ... Biotin-Linked Antibody to Calcium/Calmodulin Dependent Protein Kinase II Gamma (CAMK2g) ...
CASK: calcium/calmodulin dependent serine protein kinase. *CASQ2: calsequestrin 2. *CASR: calcium sensing receptor ... CDKN1C: cyclin dependent kinase inhibitor 1C. *CDKN1B: cyclin dependent kinase inhibitor 1B ...
The CASK gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). ... The CASK gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). The ... Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol. 2009 Oct;66(4):438-43. doi: 10.1002/ana. ... Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7, to promote ...
Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of ... Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of ... Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of ... Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of ...
Calcium/calmodulin-dependent protein kinase II (CaMKII) is certainly a synaptic, autophosphorylating kinase. Calcium/calmodulin ... Calcium mineral/calmodulin-dependent proteins kinase II (CaMKII) can be an autophosphorylating kinase (14,15) that constitutes ... dependent protein kinase II (CaMKII) is certainly a synaptic, autophosphorylating kinase thats needed for storage and learning ... adjustments in kinase/phosphatase actions, adjustments in the business of scaffolding protein, and adjustments in the ...
Identification of a Calcium/Calmodulin-dependent Protein Kinase That Phosphorylates the Neurospora Circadian Clock Protein ... Identification of a Calcium/Calmodulin-dependent Protein Kinase That Phosphorylates the Neurospora Circadian Clock Protein ... Identification of a Calcium/Calmodulin-dependent Protein Kinase That Phosphorylates the Neurospora Circadian Clock Protein ... Identification of a Calcium/Calmodulin-dependent Protein Kinase That Phosphorylates the Neurospora Circadian Clock Protein ...
MORs, μ opioid receptors; CaMKII, calcium/calmodulin-dependent protein kinase II; TrkB, tyrosine receptor kinase B; BDNF, brain ... its target calcium/calmodulin-dependent protein kinase II gamma (CaMKII γ) and CaMKII γ-dependent BDNF expression gradually ... via an extracellular signal-regulated kinase (ERK) or protein kinase A cascade signaling pathway, which then upregulated miR- ... After knocking out the β-arrestin-2 (a G protein-coupled receptor regulatory protein) gene, the analgesic effect of morphine is ...
... calcium/calmodulin-dependent protein kinase II; PKA: protein kinase A; PKC: protein kinase C; PKG: protein kinase G; NOS: ... including cAMP-dependent protein kinase (PKA), Ca+2/phospholipid-dependent protein kinase (PKC), Ca+2/calmodulin-dependent ... Abbreviations: Ca+2/CaM: Calcium/calmodulin; cGMP: cyclic guanosine monophosphate; GC: guanylate cyclase; PKG: protein kinase G ... protein kinase II (CaMKII), and (cGMP)-dependent protein kinase (PKG) (Ji et al., 2003 ; Tanabe et al., 2009 ; Wu et al., 2005 ...
Calcium/calmodulin-dependent protein kinase with a kinase domain and 2 calmodulin-like EF handsGLYCEROLMAGNESIUM ... Calcium/calmodulin-dependent Protein Kinase With a Kinase Domain and 2 Calmodulin-like EF Hands ... 3HKO: Crystal structure of a cdpk kinase domain from cryptosporidium Parvum, cgd7_40. ...
... and ASTRAL compendium for protein structure and sequence analysis ... calcium/calmodulin-dependent protein kinase. Species: Rattus ... calmodulin-dependent protein kinase from rat. Class: kinase. Keywords: kinase, signal transduction, calcium/calmodulin. ... SCOPe: Structural Classification of Proteins - extended. Release 2.08 (updated 2023-01-06, stable release September 2021) ...
Name: calcium/calmodulin-dependent protein kinase II alpha. Synonyms: alpha-CaMKII. Type: Gene ... Synonyms: Gnas1, Gs-alpha, Gs alpha, G alpha s, Nesp55, P2, P3, P1, neuroendocrine-specific Golgi protein p55 isoform 1, ... Name: transformation/transcription domain-associated protein. Synonyms: transactivation/transformation-domain associated ... Name: SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 ...
calcium/calmodulin dependent protein kinase II inhibitor 1. Intracellular. 9.5. 1.37e-7. ... transmembrane p24 trafficking protein 2. Membrane, Intracellular. 69.3. 3.36e-6. HK1. hexokinase 1. Intracellular. 41.4. 3.39e- ... The Human Protein Atlas project is funded. by the Knut & Alice Wallenberg Foundation. ... phosphatidylcholine transfer protein. Intracellular. 2.3. 3.43e-6. ZDHHC4. zinc finger DHHC-type palmitoyltransferase 4. ...
... protein kinase A; and CaMKII alpha: calcium/calmodulin-dependent protein kinase II alpha) [101, 102, 103, 104]. These kinases ... Ocular dominance plasticity is stably maintained in the absence of alpha calcium calmodulin kinase II (alphaCaMKII) ... As a second messenger, calcium activates many intracellular signaling cascades mainly including three critical kinases (ERK: ... Calcium: a second messenger. Glutamate-gated AMPA and NMDA receptors regulate intracellular calcium level. ...
Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase ... Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev. 2008;4:CD006163.DOIPubMedGoogle Scholar ... Besides age and diagnostic PCR Ct value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently ... Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently ...
ADAMTS9: ADAM metallopeptidase with thrombospondin type 1 motif 9; CAMK1D: Calcium/calmodulin-dependent protein kinase 1D; ... Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J. Biol. Chem., 281: 28858- ... This gene product is an integral membrane protein that is a G-protein coupled 7-transmembrane receptor, its predominant ... Cyclin-dependent kinase inhibitor 2A/2B; FTO: Fat mass and obesity associated; HHEX: Haematopoietically expressed homeobox; ...
calcium/calmodulin-dependent protein kinase kinase 1 Synonyms:. CaM-KK , cam-kk alpha , cam-kk1 , camkk 1 , camkka [-] ( ...
Here the authors show that protein kinase D1 is inactivated by excitotoxicity in a model of stroke and that its activation can ... that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein ... Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on ... Protein kinase D1 (PKD1), together with PKD2 and PKD3, constitute a family classified within the calcium/calmodulin-dependent ...
enables calcium-dependent protein serine/threonine kinase activity IBA Inferred from Biological aspect of Ancestor. more info ... enables calmodulin-dependent protein kinase activity IBA Inferred from Biological aspect of Ancestor. more info ... MAP kinase-activated protein kinase 2. Names. MAPK-activated protein kinase 2. MAPKAP kinase 2. NP_032577.1. *EC 2.7.11.1 ... Mapkapk2 MAP kinase-activated protein kinase 2 [Mus musculus] Mapkapk2 MAP kinase-activated protein kinase 2 [Mus musculus]. ...
Source Reference: Ozcan L, et al "Activation of calcium/calmodulin-dependent protein kinase II in obesity mediates suppression ... The improvements also occurred when they knocked out downstream processes, including p38 and MAPK-activating protein kinase 2 ( ... Mouse Studies Point to Kinase as Diabetes Treatment Target. by Kristina Fiore, Staff Writer, MedPage Today November 24, 2013 ... Although kinases can act very generally, Tabas said he and colleagues are working on an allosteric version that will more ...
The rise in intracellular calcium levels activates map kinase (MAPK) and calcium/calmodulin-dependent protein kinase II (CAMKII ... and causes the production of cAMP and the activation of protein kinase A (PKA). This receptor subtype is expressed on the ... which increases intracellular Ca2+ and activates protein kinase C (PKC). ... Ludwig, M., and Leng, G. (2006). Dendritic peptide release and peptide-dependent behaviours. Nat. Rev. Neurosci. 7, 126-136. ...
... studies have indicated that β-carotene intake alleviates brain fog through the calcium/calmodulin-dependent protein kinase IV ( ... Kinase, Language, Mental Health, Molecule, Nutrients, Pandemic, Protein, Vegetables, Vitamin A, Vitamin C, Vitamin E, Vitamins ... and protein-protein interaction networks lead to cognitive dysfunction.. Importantly, cognitive function is not stable, as it ... Tags: Aging, Alzheimers Disease, Anti-Inflammatory, Antioxidant, Beta-Carotene, Blood, Brain, Brain Fog, Calcium, Cancer, ...
Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 ... CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance. ... CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance. ...
Calcium and calcium/calmodulin-dependent serine/threonine-protein kinase DMI-3 OS=Medicago trun…. ... Protein kinase-like. 1515. 2. 118606. Recoverin. - Molecular Function: calcium ion binding (GO:0005509). Calcium-binding EF- ... Symbols: ATCPK2, CPK2 , CPK2 (CALMODULIN-DOMAIN PROTEIN KINASE CDPK ISOFORM 2); calcium- and c…. ... Protein kinase. - Molecular Function: protein kinase activity (GO:0004672). - Molecular Function: ATP binding (GO:0005524). - ...
20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin -dependent protein kinase II-induced mitogen-activated protein ... protein kinase C) and other transcription factors (nuclear factor kappa B and sterol regulatory element binding protein). ... Rozengurt, E. (2011). Protein kinase D signaling: multiple biological functions in health and disease. Physiology (Bethesda), ... Fields, A. P., & Murray, N. R. (2008). Protein kinase C isozymes as therapeuthic targets for treatment of human cancers. ...
calcium/calmodulin dependent protein kinase IV , CaMK IV , CaMK-GR , CaMKIV , caMK ... calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited ... The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/ ...
  • The CASK gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). (medlineplus.gov)
  • Calcium mineral/calmodulin-dependent proteins kinase II (CaMKII) can be an autophosphorylating kinase (14,15) that constitutes up to 2% of total proteins in certain parts of the brain and it is extremely enriched at synapses (16). (healthyguide.info)
  • CaMKII is certainly turned on by calcium-saturated calmodulin (CaM) (17), as soon as activated, it could autophosphorylate at T286 (18). (healthyguide.info)
  • This CaMKII-phosphatase program satisfies the least requirements from the autophosphorylating kinase-phosphatase program described above, which is as a result possible Rabbit Polyclonal to Parkin a bistable CaMKII change forms the molecular basis of synaptic plasticity and long-term storage (21). (healthyguide.info)
  • CaMKII activation is essential (22,23) and enough (24,25) for hippocampal NMDAR-dependent LTP, and CaMKII knockout (26C28) and knockdown (29) mice present serious deficits in?many learning duties. (healthyguide.info)
  • In a series of experiments in mice, researchers found that inhibition of the kinase CaMKII -- or even some of its downstream components -- lowered blood glucose and insulin levels, Ira Tabas, MD, PhD , of Columbia University Medical Center in New York City, and colleagues reported online in Cell Metabolism . (medpagetoday.com)
  • In the current study, they found CaMKII inhibition suppresses levels of the pseudo-kinase TRB3 to improve Akt-phosphorylation, thereby improving insulin sensitivity. (medpagetoday.com)
  • Instead, inhibiting the CaMKII pathway suppressed levels of the pseudo-kinase TRB3, which likely occurred because of suppression of ATF4 -- all of which led to an increase in Akt-phosphorylation and insulin sensitivity. (medpagetoday.com)
  • As a result, there "appear to be two separate CaMKII pathways, one involved in CaMKII-p38-FoxO1 dependent hepatic glucose production, and the other involved in defective insulin-induced p-Akt," they wrote. (medpagetoday.com)
  • Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. (umassmed.edu)
  • The CaMKII (calcium/calmodulin-dependent protein kinase II) pathway regulates key cellular processes and functions throughout the body, including retinal ganglion cells in the eye. (newswise.com)
  • For this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. (researchgate.net)
  • The dodecameric protein kinase CaMKII is expressed throughout the body. (elifesciences.org)
  • This manuscript reports the fundamental finding that an oligomeric protein kinase, CaMKII, can be phosphorylated by another molecule of the holoenzyme in a manner that does not involve subunit exchange. (elifesciences.org)
  • B ) Cartoon representation of activation of CaMKII by calcium:calmodulin (top) and proposed mechanism for spread of kinase activity (bottom). (elifesciences.org)
  • C ) Schematic representation of experiment performed in panel ( D ). ( D ) Kinase activity of CaMKII WT (10 nM) against CaMKII KD (4 μM). (elifesciences.org)
  • These included the protein extracellular signal-regulated kinase (ERK), calcium/calmodulin-dependent kinase IIα (CaMKIIα), CaMKIIβ, CaMKIV, and the cAMP-response element binding protein (CREB). (sophia.ac.jp)
  • Although emerging evidence suggests a potential role of calcium/calmodulin-dependent kinase II (CaMKII) in prostate cancer, its role in prostate cancer tumorigenesis is largely unknown. (tmu.edu.tw)
  • Genetic deletion of the b-oxidation rate-limiting enzyme ACOX family proteins decreased CaMKII activation, whereas overexpression of ACOXI increased CaMKII activation. (tmu.edu.tw)
  • We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. (nih.gov)
  • Here we report that extinction is triggered by two hippocampal signaling pathways underlying retrieval (the cAMP-dependent protein kinase and the mitogen-activated protein kinase pathways) and two other mechanisms that become activated at the same time and are not necessary for retrieval (N-methyl-D-aspartate glutamatergic receptors and the calcium/calmodulin-dependent protein kinase II signaling pathway). (unboundmedicine.com)
  • Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. (nature.com)
  • Excitotoxic production of ROS elevates death-associated protein kinase (DAPK) activity, which provokes neuronal apoptosis in cerebral ischemia and seizure models 8 . (nature.com)
  • The granule cell enriched Ca(2+)/calmodulin dependent protein kinase (Cam kinase-Gr) may serve as a calcium activated switch involved in neuronal communication. (epa.gov)
  • Based on its subcellular distribution, Cam kinase-Gr provides particular neuronal populations with a coordinated CA(2+)-signalling pathway which may regulate several aspects of neuronal function. (epa.gov)
  • The transient, activity-dependent formation of groups of holoenzymes is well suited to the speed of neuronal activity. (elifesciences.org)
  • 5-Hydroxytryptamine type 2A receptors regulate cyclic AMP accumulation in a neuronal cell line by protein kinase C-dependent and calcium/calmodulin-dependent mechanisms. (aspetjournals.org)
  • In the present study, we examined the role of protein tyrosine phosphorylation and the mitogen-activated protein kinases, ERK1/2,in mediating BK-induced AP-1 and DNA replication in cultured rat mesangial cells. (nih.gov)
  • BK (10(-9) to 10(-7) M) stimulated a rapid increase in tyrosine phosphorylation of multiple proteins with an estimated molecular mass of 120-130, 90-95, and 44-42 kDa. (nih.gov)
  • Genistein, a specific tyrosine kinase inhibitor, prevented the phosphorylation of ERK2 by BK. (nih.gov)
  • Each of these effects was blocked by tyrosine kinase inhibition with genistein or herbimycin A. Similarly, antisense oligodeoxynucleotide targeting of ERK1/2 mRNA inhibited BK-stimulated DNA synthesis. (nih.gov)
  • AP-1 pathway and that BK mitogenic signaling is critically dependent on protein tyrosine phosphorylation. (nih.gov)
  • Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102. (neurotree.org)
  • cAMP-mediated stimulation of tyrosine hydroxylase mRNA translation is mediated by polypyrimidine-rich sequences within its 3'-untranslated region and poly(C)-binding protein 2. (rochester.edu)
  • Breakthroughs from the lab have included determining the auto-inhibited structures of several tyrosine kinases, including Src family kinases and elucidating the mechanism of allosteric activation of the kinase domains of the EGF receptor. (amgen.com)
  • A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. (curehunter.com)
  • This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. (genetex.com)
  • Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C) and other transcription factors (nuclear factor kappa B and sterol regulatory element binding protein). (springer.com)
  • One such action is activation of the MAPK kinase (ERK1/ERK2) pathway. (bvsalud.org)
  • From Neurospora cell extracts, an ∼50-kDa Ca/CaM-dependent kinase (CAMK-1) that can specifically phosphorylate FRQ was purified. (elsevierpure.com)
  • In liver I/R, members of the calcium/calmodulin-dependent protein kinase (CaMK) family are known to be activated, but their individual roles are largely unknown. (usuhs.edu)
  • The CASK protein is primarily found in nerve cells (neurons) in the brain, where it helps control the activity (expression) of other genes that are involved in brain development. (medlineplus.gov)
  • Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7 , to promote development of the nerves that control eye movement (the oculomotor neural network). (medlineplus.gov)
  • The mutations that cause CASK -related intellectual disability affect the role of the CASK protein in brain development and function. (medlineplus.gov)
  • MICPCH is caused by mutations that eliminate CASK function, while mutations that impair the function of this protein cause XL-ID with or without nystagmus. (medlineplus.gov)
  • Affected individuals with nystagmus may have CASK gene mutations that disrupt the interaction between the CASK protein and the protein produced from the FRMD7 gene, leading to problems with the development of the oculomotor neural network and resulting in abnormal eye movements. (medlineplus.gov)
  • Orthologous to human MAPKAPK2 (MAPK activated protein kinase 2). (nih.gov)
  • Proinflammatory Effect of Endothelial Microparticles Is Mitochondria Mediated and Modulated Through MAPKAPK2 (MAPK-Activated Protein Kinase 2) Leading to Attenuation of Cardiac Hypertrophy. (nih.gov)
  • The improvements also occurred when they knocked out downstream processes, including p38 and MAPK-activating protein kinase 2 (MK2). (medpagetoday.com)
  • Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha promotes long-term induction of neuroprotective genes and pathways in a mouse model of Alzheimer's disease. (otago.ac.nz)
  • Calcium/calmodulin dependent protein kinase II downregulates both calcineurin and protein kinase C mediated pathways for cytokine gene transcription in human T cells. (bioacademy.gr)
  • Prostaglandin E2 and other cyclic AMP elevating agents inhibit interleukin 2 gene transcription by counteracting calcineurin-dependent pathways. (bioacademy.gr)
  • Early steps in this transition are complex, with at least 2 signaling pathways identified: 1 stops yeast growth and another, with a heat shock protein 70-type profile, initiates the assembly of proteins necessary for mycelial growth. (cdc.gov)
  • Yeast-form-specific genes identified in Histoplasma capsulatum function in calcium/calmodulin signaling pathways and sulphur metabolism. (cdc.gov)
  • Calcium-dependent signaling pathways and heat shock protein expression regulate dimorphism in Paracoccidioides brasiliensis and have broad implications for other pathogens. (cdc.gov)
  • Once there is an influx of calcium cations (Ca2+) into the muscle, either from the sarcoplasmic reticulum or from the extracellular space, contraction of smooth muscle fibres may begin. (wikipedia.org)
  • After the influx of calcium ions and the binding to calmodulin, pp60 SRC (a protein kinase)causes a conformational change in MYLK, activating it and resulting in an increase in phosphorylation of myosin light chain at serine residue 19. (wikipedia.org)
  • 2 , 3 In particular, long-term N -methyl- D -aspartate (NMDA) receptor-dependent synaptic potentiation of glutamatergic inputs onto LA principal neurons remains the leading candidate mechanism for fear memory encoding. (nature.com)
  • The alpha isoform is responsible for synaptic plasticity and participates in memory through its phosphorylation of synaptic proteins. (elifesciences.org)
  • Many types of opioid receptors (e.g., μ , κ , δ ) exist in the nervous system, and they are all typical inhibitory G protein-coupled receptors (GPCRs) [ 30 ]. (hindawi.com)
  • Regulation of calcium/calmodulin-dependent protein kinase II docking to N-methyl-D-aspartate receptors by calcium/calmodulin and alpha-actinin. (neurotree.org)
  • Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11. (aspetjournals.org)
  • A further chapter discusses how surface membrane G-protein receptors in C. albicans and other fungi transmit external stimuli through 2 major protein kinase cascades. (cdc.gov)
  • Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates a specific myosin light chain, namely, the regulatory light chain of myosin II. (wikipedia.org)
  • Similar to ROCK, Protein Kinase C regulates MYLK via the CPI-17 protein, which downregulates MYLP. (wikipedia.org)
  • Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone. (stembook.org)
  • Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. (nih.gov)
  • Cytochrome p450-dependent metabolism of ω-6 and ω-3 long-chain polyunsaturated fatty acids. (springer.com)
  • The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. (genetex.com)
  • Cam kinase-Gr is also evident in the axons of granule cells and present to a lesser extent in the cytoplasm and dendrites of these neurons. (epa.gov)
  • Antiapoptotic and trophic effects of dominant-negative forms of dual leucine zipper kinase in dopamine neurons of the substantia nigra in vivo. (rochester.edu)
  • It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. (curehunter.com)
  • Although kinases can act very generally, Tabas said he and colleagues are working on an allosteric version that will more specifically target MK2 by binding to a site that is unique to this enzyme. (medpagetoday.com)
  • A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. (bvsalud.org)
  • This enzyme is also sometimes dependent on CALCIUM. (bvsalud.org)
  • This web site could be dephosphorylated by many localized proteins phosphatases synaptically, including PP1 and PP2A (20). (healthyguide.info)
  • Several feasible molecular mechanisms have already been suggested to take into account the permanent adjustments on the synapse, including adjustments in regional transcription rates, adjustments in kinase/phosphatase actions, adjustments in the business of scaffolding protein, and adjustments in the localization/aggregation of specific protein (10,11). (healthyguide.info)
  • While short- and long-term memory formation has been associated with the phosphorylation levels of key memory-related proteins, the molecular mechanisms underlying melatonin-induced memory enhancement have remained elusive. (sophia.ac.jp)
  • His laboratory uses x-ray crystallography to determine the three-dimensional structures of proteins involved in signaling, as well as biochemical, biophysical, and cell biological analyses to elucidate mechanisms. (amgen.com)
  • Another source of smooth muscle disorders like ischemia-reperfusion, hypertension, and coronary artery disease arise when mutations to protein kinase C (PKC) result in excessive inhibition of MYLP, which counteracts the activity of MYLK by dephosphorylating myosin light chain. (wikipedia.org)
  • In contrast, protein kinase C inhibition or depletion had no effect on BK-induced c-fos mRNA, AP-1-DNA binding activity, or DNA synthesis. (nih.gov)
  • Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes. (springer.com)
  • I have a lot of experience in the following methodologies: protein isolation, protein synthesis assays, Western blotting, genotyping, RNA isolation and qPCR miRNA/mRNA arrays, bioinformatics and statistical analyses. (otago.ac.nz)
  • Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha. (otago.ac.nz)
  • On either sides of the catalytic core sit calcium ion/calmodulin binding sites. (wikipedia.org)
  • In particular, prenatal cannabinoid treatment reduced the phosphorylated levels of ERK1/2 in selected subcellular compartments of hippocampus, frontal and prefrontal cortex, whereas no changes were observed in the total levels of these proteins. (researchgate.net)
  • Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm. (springer.com)
  • Effects of tyrphostins on the activated c-src protein in NIH/3T3 cells. (aspetjournals.org)
  • To identify CAMK2D target proteins in renal collecting duct cells (mpkCCD), we deleted Camk2d and carried out LC-MS/MS-based quantitative phoshoproteomics. (bvsalud.org)
  • AQP2 protein abundance was lower in the CAMK2D knockout cells than in CAMK2D-intact controls. (bvsalud.org)
  • Taken together, our results suggest that multiple kinases may phosphorylate FRQ in vivo. (elsevierpure.com)
  • Oxidative stress is an important activator of PKD1 in cellular models, but its capacity to activate this kinase in vivo is largely unknown. (nature.com)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • If independently confirmed in the future, the study will stand as having provided a novel regulatory mechanism for the autophosphorylation of this kinase. (elifesciences.org)
  • Their structural insights have helped understand how the misregulation of these enzymes is often coupled to cancer and immune diseases and has implications for the development of kinase-targeted drugs to treat these diseases. (amgen.com)
  • His laboratory has provided a fundamental understanding of the structure and regulation several other signaling proteins, including STATs, the Ras activator SOS, and calcium/calmodulin-dependent protein kinase-II. (amgen.com)
  • Ca2+/Calmodulin-dependent protein kinase 2 (CAMK2) family proteins are involved in regulation of cellular processes in a variety of tissues including brain, heart, liver and kidney. (bvsalud.org)
  • Protein kinase D1 (PKD1), together with PKD2 and PKD3, constitute a family classified within the calcium/calmodulin-dependent protein kinase superfamily 7 . (nature.com)
  • Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). (nature.com)
  • Our results place fundamental limits on the activation mechanism of this kinase. (elifesciences.org)
  • Reducing intracellular calcium concentration inactivates MLCK but does not stop smooth muscle contraction since the myosin light chain has been physically modified through phosphorylation(and not via ATPase activity). (wikipedia.org)
  • The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. (nih.gov)
  • In this study, we showed that most of the kinase activity phosphorylating FRQ in vitro was calcium/ calmodulin-dependent, and the endogenous FRQ in the Neurospora extracts was phosphorylated by a Ca/ CaM-dependent kinase-like activity. (elsevierpure.com)
  • In vitro, this kinase accounts for near half of the FRQ kinase activity, and it can phosphorylate the FRQ region that contains the three known functionally important phosphorylation sites. (elsevierpure.com)
  • Rho kinase also modulates the activity of MYLK by downregulating the activity of MYLK's counterpart protein: Myosin Light Chain Phosphatase (MYLP). (wikipedia.org)
  • Under specific conditions, such a functional program can develop a bistable change, where at basal circumstances expresses of high and low kinase activity are both steady, as well as the?current activity condition depends on the annals of the machine (13). (healthyguide.info)
  • Enables protein serine/threonine kinase activity. (nih.gov)
  • Substrate-based kinase activity inference identifies MK2 as driver of colitis. (nih.gov)
  • The lack of equilibrium within the brain structure and disorientation at the molecular/cellular level, neural interactions, and protein-protein interaction networks lead to cognitive dysfunction. (news-medical.net)
  • Analysis of calmodulin-kinase cascade by using functional proteomics. (nii.ac.jp)
  • This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling. (nih.gov)
  • Nuclear and Axonal Localization of Ca(2+)/Calmodulin-Dependent Protein Kinase Type Gr in Rat Cerebellar Cortex. (epa.gov)
  • Binding of calcium ion to this domain increases the affinity of MYLK binding to myosin light chain. (wikipedia.org)
  • This myosin binding domain is located at the C-Terminus end of the kinase. (wikipedia.org)
  • In addition to downregulation of MYLK, ROCK indirectly strengthens actin/myosin contraction through inhibiting Cofilin, a protein which depolymerizes actin stress fibers. (wikipedia.org)
  • Because myosin light chain has no inherent phosphate cleaving property over active PKC prevents the dephosphorylation of myosin light protein leaving it in the activated conformation, causing an increase in smooth muscle contraction. (wikipedia.org)
  • The normal requirement of any molecular correlate of long-term storage is it must be steady in the current presence of proteins turnover (12), because proteins turnover moments are on the purchase of seconds to some weeks, whereas long-term recollections can last for life. (healthyguide.info)
  • A leading applicant for a long lasting molecular change that is steady to proteins turnover is something made up of an autophosphorylating kinase combined to a phosphatase (13). (healthyguide.info)
  • abstract = "Phosphorylation of circadian clock proteins represents a major regulatory step that controls circadian clocks. (elsevierpure.com)
  • Dietary fatty acids and membrane protein function. (springer.com)
  • Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)